Planta Med 2017; 83(10): 846-854
DOI: 10.1055/s-0043-104391
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Chamomile Flower, Myrrh, and Coffee Charcoal, Components of a Traditional Herbal Medicinal Product, Diminish Proinflammatory Activation in Human Macrophages

Cica Vissiennon
1   University of Leipzig, Medical Faculty, Institute of Medical Physics and Biophysics, Leipzig
3   REPHA GmbH Biologische Arzneimittel, Langenhagen
,
Dima Hammoud
1   University of Leipzig, Medical Faculty, Institute of Medical Physics and Biophysics, Leipzig
2   Institut Régional du Génie Industriel et Biotechnologiques et sciences appliquées (IRGIB-Africa), Cotonou, République du Bénin
,
Steffen Rodewald
4   University of Leipzig, Institute of Pharmacy, Leipzig
,
Karin Fester
4   University of Leipzig, Institute of Pharmacy, Leipzig
,
Karl-Heinz Goos
3   REPHA GmbH Biologische Arzneimittel, Langenhagen
,
Karen Nieber
4   University of Leipzig, Institute of Pharmacy, Leipzig
,
Jürgen Arnhold
1   University of Leipzig, Medical Faculty, Institute of Medical Physics and Biophysics, Leipzig
› Author Affiliations
Further Information

Publication History

received 24 August 2016
revised 31 January 2017

accepted 10 February 2017

Publication Date:
06 March 2017 (online)

Abstract

A traditional herbal medicinal product, containing myrrh, chamomile flower, and coffee charcoal, has been used in Germany for the relief of gastrointestinal complaints for decades. Clinical studies suggest its use in the maintenance therapy of inflammatory bowel disease. However, the pharmacological mechanisms underlying the clinical effects are not yet fully understood.

The present study aims to elucidate immunopharmacological activities of myrrh, chamomile flower, and coffee charcoal by studying the influence of each plant extract on gene expression and protein release of activated human macrophages.

The plant extracts effect on gene and protein expression of activated human monocyte-derived macrophages was investigated by microarray gene expression analysis and assessment of the release of pro- and anti-inflammatory mediators (TNFα, chemokine CXCL13, and interleukin-10) using an ELISA test system.

The extracts of myrrh, chamomile flower, and coffee charcoal influenced gene expression of activated human macrophages within the cytokine/chemokine signaling pathway. Particularly, chemokine gene expression was suppressed. Subsequently, the production of CXCL13 and, to a minor extent, cytokine TNFα was inhibited by all herbal extracts. Chamomile flower and coffee charcoal extracts enhanced interleukin-10 release from activated macrophages. The observed effects on protein release were comparable to the effect of budesonide, which decreased TNFα and CXCL13 and enhanced interleukin-10 release.

The components of the herbal medicinal product influence the activity of activated human macrophages on both gene and protein level. The induced alterations within chemokine/cytokine signaling could contribute to a positive effect on the immunological homeostasis, which is disturbed in patients with chronic intestinal inflammation.

Supporting Information

HPLC chromatograms and LC-MS data as well as hierarchical figures of gene ontological enrichment analysis and tables with expression values of differentially expressed genes are available as Supporting Information.

 
  • References

  • 1 Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14: 329-342
  • 2 Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 2000; 6: 21-33
  • 3 Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, Korzenik J. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis 2015; 9: 86-106
  • 4 Hilsden RJ, Verhoef MJ, Rasmussen H, Porcino A, DeBruyn JCC. Use of complementary and alternative medicine by patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17: 655-662
  • 5 Ng SC, Lam YT, Tsoi KKF, Chan FKL, Sung JJY, Wu JCY. Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38: 854-863
  • 6 Albrecht U, Müller V, Schneider B, Stange R. Efficacy and safety of a herbal medicinal product containing myrrh, chamomile and coffee charcoal for the treatment of gastrointestinal disorders: a non-interventional study. BMJ Open Gastroenterol 2015; 1: e000015
  • 7 Stange R, Koch B, Seidel C, Bühring M. Günstiger Verlauf einer schweren Colitis ulcerosa. Forsch Komplementmed 2004; 5: 296-299
  • 8 Gruia FS. Das Phytotherapeutikum Myrrhinil-Intest® bei unspezifischen Darmerkrankungen. Erfahrungsheilkunde 1987; 2: 77-82
  • 9 Langhorst J, Varnhagen I, Schneider SB, Albrecht U, Rueffer A, Stange R, Michalsen A, Dobos GJ. Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis – a double-blind, double-dummy study. Aliment Pharmacol Ther 2013; 38: 490-500
  • 10 Luster AD. Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436-445
  • 11 Karp LC, Shanahan F, Targan SR. Inflammatory Bowel Disease: from Bench to Bedside. Norwell: Springer Science + Business Media, Inc.; 2005
  • 12 Carlsen HS, Baekkevold ES, Morton HC, Haraldsen G, Brandtzaeg P. Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis. Blood 2004; 104: 3021-3027
  • 13 Ansel K, Cyster JG. Chemokines in lymphopoiesis and lymphoid organ development. Curr Opin Immunol 2001; 13: 172-179
  • 14 Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993; 75: 263-274
  • 15 Schmit A, Carol M, Robert F, Bontems P, Houben JJ, van Gossum A, Goldman M, Mascart F. Dose-effect of interleukin-10 and its immunoregulatory role in Crohnʼs disease. Eur Cytokine Netw 2002; 13: 298-305
  • 16 Barbara G, Xing Z, Hogaboam CM, Gauldie J, Collins SM. Interleukin 10 gene transfer prevents experimental colitis in rats. Gut 2000; 46: 344-349
  • 17 Herfarth HH, Böcker U, Janardhanam R, Sartor RB. Subtherapeutic corticosteroids potentiate the ability of interleukin 10 to prevent chronic inflammation in rats. Gastroenterology 1998; 115: 856-865
  • 18 Schreiber S, Fedorak RN, Nielsen OH, Wild G, Williams CN, Nikolaus S, Jacyna M, Lashner BA, Gangl A, Rutgeerts P, Isaacs K, van Deventer SJ, Koningsberger JC, Cohard M, LeBeaut A, Hanauer SB. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohnʼs disease. Crohnʼs Disease IL-10 Cooperative Study Group. Gastroenterology 2000; 119: 1461-1472
  • 19 Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G, Hanauer SB, Kilian A, Cohard M, LeBeaut A, Feagan B. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohnʼs disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 2000; 119: 1473-1482
  • 20 Colombel JF, Rutgeerts P, Malchow H, Jacyna M, Nielsen OH, Rask-Madsen J, van Deventer S, Ferguson A, Desreumaux P, Forbes A, Geboes K, Melani L, Cohard M. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohnʼs disease. Gut 2001; 49: 42-46
  • 21 Herfarth H, Schölmerich J. IL-10 therapy in Crohnʼs disease: at the crossroads. Treatment of Crohnʼs disease with the anti-inflammatory cytokine interleukin 10. Gut 2002; 50: 146-147
  • 22 Jaguin M, Houlbert N, Fardel O, Lecureur V. Polarization profiles of human M-CSF-generated macrophages and comparison of M1-markers in classically activated macrophages from GM-CSF and M-CSF origin. Cell Immunol 2013; 281: 51-61
  • 23 Zhang B, Kirov S, Snoddy J. WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res 2005; 33: 741-748
  • 24 Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000; 25: 25-29
  • 25 Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28: 27-30
  • 26 Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 1980; 26: 171-176
  • 27 Chanput W, Mes JJ, Savelkoul HFJ, Wichers HJ. Characterization of polarized THP-1 macrophages and polarizing ability of LPS and food compounds. Food Funct 2013; 4: 266-276